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Clinical and Diagnostic Laboratory Immunology, July 1998, p. 438-445, Vol. 5, No. 4
1071-412X/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.

Inducible Nitric Oxide Synthase and Nitrotyrosine Are Found in Monocytes/Macrophages and/or Astrocytes in Acute, but Not in Chronic, Multiple Sclerosis

Emilia L. Oleszak,1,2,* Ewa Zaczynska,1 Meena Bhattacharjee,3 Catalin Butunoi,4 Agustin Legido,5 and Christos D. Katsetos6

Fels Institute for Cancer Research and Molecular Biology,1 Departments of Biochemistry and Neurology,2 and Department of Microbiology and Immunology,6 Temple University School of Medicine, and Section of Pediatric Neurology, St. Christopher's Hospital for Children, Allegheny University of the Health Sciences,5 Philadelphia, Pennsylvania; Department of Pathology, Baylor College of Medicine, Houston, Texas3; and Rocky Mountain Multiple Sclerosis Center, Englewood, Colorado4

Received 13 January 1998/Returned for modification 2 March 1998/Accepted 18 March 1998

We have examined the localization of inducible nitric oxide synthase (iNOS) and nitrotyrosine (the product of nitration of tyrosine by peroxynitrite, a highly reactive derivative of nitric oxide [NO]) in demyelinating lesions from (i) two young adult patients with acute multiple sclerosis (MS), (ii) a child with MS (consistent with diffuse sclerosis), and (iii) five adult patients with chronic MS. Previous reports have suggested a possible correlation between iNOS, peroxynitrite, related nitrogen-derived oxidants, and the demyelinating processes in MS. We have demonstrated iNOS-immunoreactive cells in both acute-MS and diffuse-sclerosis-type lesions. In acute-MS lesions, iNOS was localized in both monocytes/macrophages and reactive astrocytes. However, foamy (myelin-laden) macrophages and the majority of reactive astrocytes were iNOS negative. In specimens from the childhood MS patient, iNOS protein was present only in a subpopulation of reactive or hypertrophic astrocytes. In contrast, no iNOS staining was detected in chronic-MS lesions. Immunohistochemical staining of acute-MS lesions with an antibody to nitrotyrosine revealed codistribution of iNOS- and nitrotyrosine-positive cells, although nitrotyrosine staining was more widespread in cells of the monocyte/macrophage lineage. In diffuse-sclerosis-type lesions, nitrotyrosine staining was present in hypertrophic astrocytes, whereas it was absent in chronic-MS lesions. These results suggest that NO and nitrogen-derived oxidants may play a role in the initiation of demyelination in acute-MS lesions but not in the later phase of the disease.

* Corresponding author. Mailing address: Fels Institute for Cancer Research and Molecular Biology, Temple University School of Medicine, 3309 North Broad St., Philadelphia, PA 19140. Phone: (215) 707-7657. Fax: (215) 829-1320.

Clinical and Diagnostic Laboratory Immunology, July 1998, p. 438-445, Vol. 5, No. 4
1071-412X/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.


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